Article Figures & Data
Figures
- Figure 1.
Induction of LTP by a single episode versus multiple episodes of TBS. A, Recording of field EPSPs in the optic tectum. Traces of the fEPSP elicited by electric stimulation of the optic nerve (“S”) in the contralateral eye (current pulse width, 0.1 ms). Middle, Black, Averaged fEPSP in normal Ringer's solution; dark gray, after perfusion with NBQX (10 μm); dashed, after clearance of NBQX. Right, Black, Averaged fEPSP in Ringer's solution; dark gray, after perfusion with TTX (0.1 μm); dashed, recorded when electrode was outside the tectum. The arrows mark various components of the field potential: stimulation artifact (“1”), presynaptic afferent volleys for fibers of different conduction velocities (“2” and “3”), and AMPAR-mediated fEPSP (“4”). Calibration: 0.05 mV, 5 ms. B, An example showing changes of fEPSP slopes (20–80% of rising phase) over 4 h, normalized by the mean value during the first 30 min. Gray circles, Raw values of the fEPSP evoked by test stimuli at 30 s interval; filled circles, average over 5 min period. Traces above, Averaged trace of 20 fEPSPs at the time marked by numbers. Calibration: 0.1 mV, 10 ms. C, Summary of experiments shown in B. n, Total number of experiments. D, E, Same as B and C, except the application of a single episode of TBS at 0 min (arrow). F, G, Same as B and C, except that three episodes of TBS (marked by arrows) were applied at 5 min intervals.
- Figure 2.
L-LTP requires protein synthesis and gene transcription. A, Summary results showing changes of fEPSP slopes before and after three episodes of TBS (spaced by 5 min) when protein translation inhibitor anisomycin (25 μm) was applied to the bath solution for 40 min, beginning at 10 min before the induction protocol (as indicated by the shadowed bar). The value of fEPSP slope represents the average over 5 min bins. The E-LTP was not affected (1.32 ± 0.08; n = 7), but L-LTP was abolished (0.96 ± 0.06; p = 0.009 vs E-LTP, paired t test). B, Similar to A, except that the gene transcription inhibitor actinomycin D (25 μm) was applied instead of anisomycin. Averaged amplitudes of E-LTP and L-LTP were 1.22 ± 0.07 and 1.00 ± 0.09 (n = 5; p = 0.05, E-LTP vs L-LTP), respectively.
- Figure 3.
L-LTP stability depends on the interval of spaced TBS. A–D, Summary results showing changes of fEPSP slopes before and after that three episodes of TBS were applied en masse (5 s intervals) (A), at 2.5 min (B), 10 min (C), or 15 min (D) intervals. The value of fEPSP slope represents the average over 5 min bins. E, F, Cumulative distribution of the magnitude of E-LTP and L-LTP, defined by the average fEPSP slope at 10–40 and 150–180 min after the last TBS, respectively, induced by three episodes of TBS with different intervals. Significant difference was only found for L-LTP between the 5 and 15 min intervals (p = 0.02, Kolmogorov–Smirnov test). G, Average magnitude (±SEM) of E-LTP and L-LTP induced by three episodes of TBS with the interval of 0, 2.5, 5, 10, or 15 min. *p = 0.03; **p = 0.01; paired t test.
- Figure 4.
Postinduction NMDAR activation is required for L-LTP. A, Blockade of LTP induction by 30 min local perfusion of the tectum with d-AP5 (100 μm; marked by the shadow), beginning at 10 min before the spaced TBS (at 5 min interval). B–D, Effects of 15 min local perfusion of the tectum with d-AP5, beginning at 1, 15, and 45 min after termination of the last episode of the spaced TBS, respectively. E, Histograms depict the magnitude (mean ± SEM) of E-LTP and L-LTP induced by the spaced TBS, under the condition of d-AP5 perfusion at different times. The same data set as in A–D. Significant difference is marked by a double asterisk (**) (p < 0.01, paired t test). F, Effect of 15 min perfusion of the tectum with d-AP5, beginning at 1 min after a single TBS.
- Figure 5.
Requirement of postinduction Ca2+ elevation for L-LTP. A, B, Changes of fEPSP slope before and after the spaced TBS (with 5 min interval) when 30 min local perfusion of the tectum with EGTA-AM (50 μm) immediately (A) or 60 min (B) after the last episode of the spaced TBS. C, Similar to A except that the tectum was perfused locally for 30 min with the L-VGCC blocker nimodipine (20 μm) immediately after the last episode of the spaced TBS.
- Figure 6.
Postinduction activation of CP-AMPARs is not required for L-LTP. A, Dose-dependent effect of a selective CP-AMPAR antagonist IEM-1460 in reducing the fEPSP slope. The fEPSP slopes were normalized by the average slope value before the drug application (by local perfusion to the tectum for 15 min). B, Reversibility of IEM-1460 effect on the basal fEPSP slopes. The shadowed bar indicates the duration of local perfusion of IEM-1480 (100 μm). C, Changes of fEPSP slope before and after the spaced TBS (with 5 min interval) when 30 min local perfusion of the tectum with IEM-1460 (100 μm) immediately after the last episode of the spaced TBS. D–F, Same set of experiments as A–C except for another specific CP-AMPAR antagonist NASPM was used. The concentration of NASPM in E and F was at 50 μm.
- Figure 7.
L-LTP stability is unaffected by postinduction test stimulation. A, Changes of fEPSP slope before and after three episodes of TBS (spaced with 5 min interval), in the absence of low-frequency test stimulation for 45 min after the last episode of TBS. Averaged amplitude of L-LTP (at 160–190 min after the last episode of TBS) was 1.28 ± 0.08 (n = 6; mean ± SEM). B, Similar experiments as shown in A except that the tectum was perfused locally for 15 min with d-AP5 immediately after the last TBS episode. Averaged magnitude of L-LTP, 0.95 ± 0.06 (n = 5).
- Figure 8.
Postinduction spontaneous neuronal spiking in the tectum is required for L-LTP. A–C, Changes of the fEPSP slope before and after three episodes of TBS (spaced at 5 min) when the tectum was locally perfused for 15 min with TTX (25 nm), in the absence of the spaced TBS (A), and immediately (B) or 60 min (C) after the last TBS of the spaced TBS. Shown is averaged magnitude of normalized fEPSP slope over 160–190 min. B, 1.03 ± 0.09 (p = 0.75 vs the baseline, paired t test). C, 1.45 ± 0.18 (p = 0.96 vs E-LTP). D, Similar to B except that TTX (25 nm) was locally perfused to the retina. L-LTP magnitude, 1.30 ± 0.11 (p = 0.05 vs the baseline).
